U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry MIXED
Molecular Formula C18H25N3O2
Molecular Weight 315.4107
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 6
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SAXAGLIPTIN ANHYDROUS

SMILES

C1C2([H])CC3(CC1([H])CC(C2)(C3)O)[C@@]([H])(C(=O)N4[C@@]([H])(C[C@]5([H])C[C@@]54[H])C#N)N

InChI

InChIKey=QGJUIPDUBHWZPV-SGTAVMJGSA-N
InChI=1S/C18H25N3O2/c19-8-13-2-12-3-14(12)21(13)16(22)15(20)17-4-10-1-11(5-17)7-18(23,6-10)9-17/h10-15,23H,1-7,9,20H2/t10?,11?,12-,13+,14+,15-,17?,18?/m1/s1

HIDE SMILES / InChI

Molecular Formula C18H25N3O2
Molecular Weight 315.4107
Charge 0
Count
Stereochemistry MIXED
Additional Stereochemistry No
Defined Stereocenters 4 / 6
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: https://www.drugs.com/monograph/saxagliptin-hydrochloride.html

Saxagliptin is an orally active hypoglycemic (anti-diabetic drug) of the new dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. FDA approved on July 31, 2009. Saxagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor antidiabetic for the treatment of type 2 diabetes. DPP-4 inhibitors are a class of compounds that work by affecting the action of natural hormones in the body called incretins. Incretins decrease blood sugar by increasing consumption of sugar by the body, mainly through increasing insulin production in the pancreas, and by reducing production of sugar by the liver. [Bristol-Myers Squibb Press Release] DPP-4 is a membrane associated peptidase which is found in many tissues, lymphocytes and plasma. DPP-4 has two main mechanisms of action, an enzymatic function and another mechanism where DPP-4 binds adenosine deaminase, which conveys intracellular signals via dimerization when activated. Saxagliptin forms a reversible, histidine-assisted covalent bond between its nitrile group and the S630 hydroxyl oxygen on DPP-4. The inhibition of DPP-4 increases levels active of glucagon like peptide 1 (GLP-1), which inhibits glucagon production from pancreatic alpha cells and increases production of insulin from pancreatic beta cells.

Originator

Curator's Comment:: # Bristol-Myers Squibb

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
30.3000000000000007 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Onglyza

Approved Use

Diabetes mellitus, type 2: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (noninsulin dependent, NIDDM) as monotherapy or in combination therapy.

Launch Date

1248912000000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
24 ng/mL
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SAXAGLIPTIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
78 ng × h/mL
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SAXAGLIPTIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.5 h
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SAXAGLIPTIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
100%
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SAXAGLIPTIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
10 mg 1 times / day steady, oral
Highest studied dose
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
Disc. AE: Adverse event...
AEs leading to
discontinuation/dose reduction:
Adverse event (5.1%)
Sources:
2.5 mg 1 times / day steady, oral
Recommended
Dose: 2.5 mg, 1 times / day
Route: oral
Route: steady
Dose: 2.5 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Disc. AE: Lymphopenia, Rash...
AEs leading to
discontinuation/dose reduction:
Lymphopenia (0.1%)
Rash (0.2%)
Blood creatinine increased (0.3%)
Blood creatine phosphokinase increased (0.1%)
Sources:
5 mg 1 times / day steady, oral
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: steady
Dose: 5 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Disc. AE: Lymphopenia, Rash...
AEs leading to
discontinuation/dose reduction:
Lymphopenia (0.5%)
Rash (0.3%)
Blood creatine phosphokinase increased (0.2%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Adverse event 5.1%
Disc. AE
10 mg 1 times / day steady, oral
Highest studied dose
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
Blood creatine phosphokinase increased 0.1%
Disc. AE
2.5 mg 1 times / day steady, oral
Recommended
Dose: 2.5 mg, 1 times / day
Route: oral
Route: steady
Dose: 2.5 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Lymphopenia 0.1%
Disc. AE
2.5 mg 1 times / day steady, oral
Recommended
Dose: 2.5 mg, 1 times / day
Route: oral
Route: steady
Dose: 2.5 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Rash 0.2%
Disc. AE
2.5 mg 1 times / day steady, oral
Recommended
Dose: 2.5 mg, 1 times / day
Route: oral
Route: steady
Dose: 2.5 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Blood creatinine increased 0.3%
Disc. AE
2.5 mg 1 times / day steady, oral
Recommended
Dose: 2.5 mg, 1 times / day
Route: oral
Route: steady
Dose: 2.5 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Blood creatine phosphokinase increased 0.2%
Disc. AE
5 mg 1 times / day steady, oral
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: steady
Dose: 5 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Rash 0.3%
Disc. AE
5 mg 1 times / day steady, oral
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: steady
Dose: 5 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Lymphopenia 0.5%
Disc. AE
5 mg 1 times / day steady, oral
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: steady
Dose: 5 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
inconclusive
no
no
no
no
no
no
no
no
no
no
no (co-administration study)
Comment: administration with simvastatin did not alter PK of metformin; administration with diltiazem increased the plasma Cmax of diltiazem by 16%, AUC of diltiazem was unchagned
Page: 17
no
no (co-administration study)
Comment: administration with simvastatin did not alter PK of metformin; administration with diltiazem increased the plasma Cmax of diltiazem by 16%, AUC of diltiazem was unchanged; administration with ketoconazole decreased Cmax and AUC of ketoconazole by 16% and 13%, respectively;
Page: 17
no
no (co-administration study)
Comment: administration with metformin did not alter PK of metformin
Page: 16
no
no (co-administration study)
no
no (co-administration study)
no
unlikely (co-administration study)
Comment: no concentration and time-dependent inhibtion; administration with pioglitazone increased the plasma Cmax of glyburide by 14%, AUC was unchanged.
Page: 39
no
unlikely (co-administration study)
Comment: no concentration and time-dependent inhibtion; administration with glyburide increased the plasma Cmax of glyburide by 16%, AUC was unchanged.
Page: 39
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
yes (co-administration study)
Comment: ketoconazole increased the Cmax for saxagliptin by 62% and the AUC by 2.5-fold
Page: 38,42
minor
minor
minor
no
no
no
no
no
no
no
no
yes
no (co-administration study)
Comment: administration with digoxin did not alter PK of saxagliptin
Page: 39
Tox targets

Tox targets

Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
(R)-8-(3-amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione (BI 1356), a novel xanthine-based dipeptidyl peptidase 4 inhibitor, has a superior potency and longer duration of action compared with other dipeptidyl peptidase-4 inhibitors.
2008 Apr
Antihyperglycemic effects of ASP8497 in streptozotocin-nicotinamide induced diabetic rats: comparison with other dipeptidyl peptidase-IV inhibitors.
2009 Sep-Oct
Patents

Sample Use Guides

Diabetes Mellitus
Route of Administration: Oral
Saxagliptin inhibited rat plasma DPP-IV activity in vitro with an IC(50) value of 2.00 nmol/l
Substance Class Chemical
Created
by admin
on Sat Jun 26 05:04:13 UTC 2021
Edited
by admin
on Sat Jun 26 05:04:13 UTC 2021
Record UNII
8I7IO46IVQ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
SAXAGLIPTIN ANHYDROUS
Common Name English
SAXAGLIPTIN [MI]
Common Name English
SAXAGLIPTIN [INN]
Common Name English
SAXAGLIPTIN [WHO-DD]
Common Name English
BMS-477118
Code English
(1S,3S,5S)-2-((2S)-AMINO(3-HYDROXYTRICYCLO(3.3.1.1(SUP 3,7))DEC-1-YL)ACETYL)-2-AZABICYCLO(3.1.0)HEXANE-3-CARBONITRILE
Systematic Name English
2-AZABICYCLO(3.1.0)HEXANE-3-CARBONITRILE, 2-((2S)-AMINO(3-HYDROXYTRICYCLO(3.3.1.1(SUP 3,7))DEC-1-YL)ACETYL), (1S,3S,5S)-
Common Name English
Classification Tree Code System Code
NDF-RT N0000175913
Created by admin on Sat Jun 26 05:04:14 UTC 2021 , Edited by admin on Sat Jun 26 05:04:14 UTC 2021
NCI_THESAURUS C98086
Created by admin on Sat Jun 26 05:04:14 UTC 2021 , Edited by admin on Sat Jun 26 05:04:14 UTC 2021
WHO-ATC A10BH03
Created by admin on Sat Jun 26 05:04:14 UTC 2021 , Edited by admin on Sat Jun 26 05:04:14 UTC 2021
NDF-RT N0000175912
Created by admin on Sat Jun 26 05:04:14 UTC 2021 , Edited by admin on Sat Jun 26 05:04:14 UTC 2021
Code System Code Type Description
FDA UNII
8I7IO46IVQ
Created by admin on Sat Jun 26 05:04:14 UTC 2021 , Edited by admin on Sat Jun 26 05:04:14 UTC 2021
PRIMARY
INN
8577
Created by admin on Sat Jun 26 05:04:14 UTC 2021 , Edited by admin on Sat Jun 26 05:04:14 UTC 2021
PRIMARY
CAS
361442-04-8
Created by admin on Sat Jun 26 05:04:14 UTC 2021 , Edited by admin on Sat Jun 26 05:04:14 UTC 2021
PRIMARY
PUBCHEM
11243969
Created by admin on Sat Jun 26 05:04:14 UTC 2021 , Edited by admin on Sat Jun 26 05:04:14 UTC 2021
PRIMARY
RXCUI
1546030
Created by admin on Sat Jun 26 05:04:14 UTC 2021 , Edited by admin on Sat Jun 26 05:04:14 UTC 2021
PRIMARY RxNorm
NCI_THESAURUS
C75984
Created by admin on Sat Jun 26 05:04:14 UTC 2021 , Edited by admin on Sat Jun 26 05:04:14 UTC 2021
PRIMARY
HSDB
8199
Created by admin on Sat Jun 26 05:04:14 UTC 2021 , Edited by admin on Sat Jun 26 05:04:14 UTC 2021
PRIMARY
MERCK INDEX
M9795
Created by admin on Sat Jun 26 05:04:14 UTC 2021 , Edited by admin on Sat Jun 26 05:04:14 UTC 2021
PRIMARY Merck Index
EVMPD
SUB25220
Created by admin on Sat Jun 26 05:04:14 UTC 2021 , Edited by admin on Sat Jun 26 05:04:14 UTC 2021
PRIMARY
EPA CompTox
361442-04-8
Created by admin on Sat Jun 26 05:04:14 UTC 2021 , Edited by admin on Sat Jun 26 05:04:14 UTC 2021
PRIMARY
DRUG BANK
DB06335
Created by admin on Sat Jun 26 05:04:14 UTC 2021 , Edited by admin on Sat Jun 26 05:04:14 UTC 2021
PRIMARY
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ACTIVE MOIETY
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